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Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis

Lookup NU author(s): Dr Helen PhillipsORCiD, Catherine Stothard, Dr Wasay Shaikh Qureshi, Dr Alberto Briones Leon, Ramada Khasawneh, Rachel Sanders, Chloe O'Loughlin, Dr Silvia Mazzotta, Rebecca Dodds, Kerstin Seidel, Dr Timothy Bates, Dr Mitsushiro Nakatomi, Dr Simon CockellORCiD, Dr Ralf KistORCiD, Dr Heiko Peters, Dr Simon BamforthORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Developmental defects affecting the heart and aortic arch arteries are a significant phenotype observed in 22q11 deletion syndrome patients and are caused by a microdeletion on chromosome 22q11. TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key gene, when mutated, for the arch artery defects. Pax9 is expressed in the pharyngeal endoderm and is downregulated in Tbx1 mutant mice. We show here that Pax9 deficient mice are born with complex cardiovascular malformations affecting the outflow tract and aortic arch arteries with failure of the 3rd and 4th pharyngeal arch arteries to form correctly. Transcriptome analysis indicated that Pax9 and Tbx1 may function together, and mice double heterozygous for Tbx1/Pax9 presented with a significantly increased incidence of interrupted aortic arch when compared to Tbx1 heterozygous mice. Using a novel Pax9Cre allele we demonstrated that the site of this Tbx1-Pax9 genetic interaction is in the pharyngeal endoderm, therefore revealing that a Tbx1-Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for critical tissue interactions during normal morphogenesis of the pharyngeal arch artery system.

Publication metadata

Author(s): Phillips HM, Stothard CA, Shaikh Qureshi WM, Kousa AI, BrionesLeon JA, Khasawneh RR, Sanders R, O'Loughlin C, Mazzotta S, Dodds R, Seidel K, Bates T, Nakatomi M, Cockell SJ, Schneider JE, Mohun TJ, Maehr R, Kist R, Peters H, Bamforth SD

Publication type: Article

Publication status: Published

Journal: Development

Year: 2019

Volume: 146

Print publication date: 23/09/2019

Online publication date: 23/08/2019

Acceptance date: 14/08/2019

Date deposited: 04/09/2019

ISSN (print): 0950-1991

ISSN (electronic): 1477-9129

Publisher: Company of Biologists Ltd


DOI: 10.1242/dev.177618

PubMed id: 31444215


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Funder referenceFunder name
PG/16/39/32115British Heart Foundation